Transcriptomics-informed large-scale cortical model captures topography of pharmacological neuroimaging effects of LSD
eLife – July 12, 2021
Source: OpenAlex
Summary
A compelling neuroscience finding reveals the biological mechanism behind Lysergic acid diethylamide (LSD)'s effects on the human brain. Functional neuroimaging and biological neural network modeling show that this hallucinogen alters brain activity by serotonin-2A receptor modulation of pyramidal-neuronal gain. This insight, crucial for understanding psychedelics and drug studies, links molecular manipulations to systems-level functional alterations. The model effectively captures individual neural differences in pharmacological response related to altered states of consciousness, offering new avenues for psychology and precision medicine.
Abstract
Psychoactive drugs can transiently perturb brain physiology while preserving brain structure. The role of physiological state in shaping neural function can therefore be investigated through neuroimaging of pharmacologically induced effects. Previously, using pharmacological neuroimaging, we found that neural and experiential effects of lysergic acid diethylamide (LSD) are attributable to agonism of the serotonin-2A receptor (Preller et al., 2018). Here, we integrate brain-wide transcriptomics with biophysically based circuit modeling to simulate acute neuromodulatory effects of LSD on human cortical large-scale spatiotemporal dynamics. Our model captures the inter-areal topography of LSD-induced changes in cortical blood oxygen level-dependent (BOLD) functional connectivity. These findings suggest that serotonin-2A-mediated modulation of pyramidal-neuronal gain is a circuit mechanism through which LSD alters cortical functional topography. Individual-subject model fitting captures patterns of individual neural differences in pharmacological response related to altered states of consciousness. This work establishes a framework for linking molecular-level manipulations to systems-level functional alterations, with implications for precision medicine.